Production and characterisation of stabilised PV-3 virus-like particles using Pichia pastoris

DOI: 10.3390/v14102159

Authors: Lee Sherry (University of Leeds) , Keith Grehan (University of Leeds) , Jessica J. Swanson (University of Leeds) , Mohammad W. Bahar (University of Oxford) , Claudine Porta (University of Oxford) , Elizabeth E. Fry (University of Oxford) , David I. Stuart (University of Oxford; Diamond Light Source) , David J. Rowlands (University of Leeds) , Nicola J. Stonehouse (University of Leeds)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Viruses , VOL 14

State: Published (Approved)
Published: October 2022

Abstract: Following the success of global vaccination programmes using the live-attenuated oral and inactivated poliovirus vaccines (OPV and IPV), wild poliovirus (PV) is now only endemic in Afghanistan and Pakistan. However, the continued use of these vaccines poses potential risks to the eradication of PV. The production of recombinant PV virus-like particles (VLPs), which lack the viral genome offer great potential as next-generation vaccines for the post-polio world. We have previously reported production of PV VLPs using Pichia pastoris, however, these VLPs were in the non-native conformation (C Ag), which would not produce effective protection against PV. Here, we build on this work and show that it is possible to produce wt PV-3 and thermally stabilised PV-3 (referred to as PV-3 SC8) VLPs in the native conformation (D Ag) using Pichia pastoris. We show that the PV-3 SC8 VLPs provide a much-improved D:C antigen ratio as compared to wt PV-3, whilst exhibiting greater thermostability than the current IPV vaccine. Finally, we determine the cryo-EM structure of the yeast-derived PV-3 SC8 VLPs and compare this to previously published PV-3 D Ag structures, highlighting the similarities between these recombinantly expressed VLPs and the infectious virus, further emphasising their potential as a next-generation vaccine candidate for PV.

Journal Keywords: poliovirus; vaccine; virus-like particle; Pichia pastoris

Diamond Keywords: Poliomyelitis; Viruses

Subject Areas: Biology and Bio-materials, Medicine


Technical Areas:

Added On: 31/10/2022 11:30

Documents:
viruses-14-02159-v2.pdf

Discipline Tags:

Vaccines Pathogens Infectious Diseases Health & Wellbeing Life Sciences & Biotech

Technical Tags: